Hemdan Dalia Ismaeil Ibrahim, Hirasaka Katsuya, Nakao Reiko, Kohno Shohei, Kagawa Sachiko, Abe Tomoki, Harada-Sukeno Akiko, Okumura Yuushi, Nakaya Yutaka, Terao Junji, Nikawa Takeshi
Department of Nutritional Physiology, Institute of Health Biosciences, the University of Tokushima Graduate School, Japan.
J Med Invest. 2009 Feb;56(1-2):26-32. doi: 10.2152/jmi.56.26.
Oxidative stress is a key factor in stimulating the expression of atrogenes, which are muscle atrophy-related ubiquitin ligases, in skeletal muscle, and it induces muscle atrophy during unloading. However, the effects of antioxidative nutrients on atrogene expression have not been demonstrated. We report on the inhibitory effects of polyphenols, such as epicatechin (EC), epicatechin gallate (ECg) and epigallocatechin gallate (EGCg) and quercetin, on atrogene expression up-regulated by three dimensional (3D)-clinorotation or glucocorticoid. These treatments markedly elevated the expression of atrogenes, including atrogin-1 and MuRF-1, in mouse C2C12 myoblasts and myotubes. Interestingly, EC, ECg, EGCg and quercetin significantly decreased the expression of atrogin-1 and MuRF-1 up-regulated by 3D-clinorotation, whereas they hardly affected atrogene expression induced by dexamethasone. ERK signaling is a well known MAPK pathway to mediate oxidative stress. Therefore, we also investigated the effect of these polyphenols on phosphorylation of ERK in C2C12 myotubes. As expected, EC, ECg, EGCg, and quercetin significantly suppressed phosphorylation of ERK, corresponding to the up-regulation of atrogenes induced by 3D-clinorotation. These results suggest that antioxidative nutrients, such as catechins and quercetin, suppress atrogene expression in skeletal muscle cells, possibly through the inhibition of ERK signaling. Thus, catechins and quercetin may prevent unloading-mediated muscle atrophy.
氧化应激是刺激骨骼肌中促萎缩基因（与肌肉萎缩相关的泛素连接酶）表达的关键因素，并且在失重期间会诱导肌肉萎缩。然而，抗氧化营养素对促萎缩基因表达的影响尚未得到证实。我们报告了表儿茶素（EC）、表儿茶素没食子酸酯（ECg）、表没食子儿茶素没食子酸酯（EGCg）和槲皮素等多酚对三维（3D）-clinorotation或糖皮质激素上调的促萎缩基因表达的抑制作用。这些处理显著提高了小鼠C2C12成肌细胞和肌管中包括atrogin-1和MuRF-1在内的促萎缩基因的表达。有趣的是，EC、ECg、EGCg和槲皮素显著降低了3D-clinorotation上调的atrogin-1和MuRF-1的表达，而它们对由地塞米松诱导的促萎缩基因表达几乎没有影响。ERK信号通路是介导氧化应激的著名丝裂原活化蛋白激酶（MAPK）途径。因此，我们还研究了这些多酚对C2C12肌管中ERK磷酸化的影响。正如预期的那样，EC、ECg、EGCg和槲皮素显著抑制了ERK的磷酸化，这与3D-clinorotation诱导的促萎缩基因上调相对应。这些结果表明，儿茶素和槲皮素等抗氧化营养素可能通过抑制ERK信号通路来抑制骨骼肌细胞中促萎缩基因的表达。因此，儿茶素和槲皮素可能预防失重介导的肌肉萎缩。
